Sermonix Pharmaceuticals’ Lasofoxifene Demonstrates Anti-Estrogen Therapy Increases Immunotherapy Efficacy by Promoting Antitumor Activity of Eosinophils

Sermonix Pharmaceuticals Inc. recently announced its lead investigational drug, lasofoxifene, was featured in a new Duke Cancer Institute study revealing that anti-estrogen therapy increases the efficacy of immunotherapy by promoting antitumor activity of eosinophils, a type of white blood cell that can influence the efficacy of immune checkpoint blockers. The findings were published Sept. 27 in the open-access, peer-reviewed journal Science Advances.

“Sermonix is excited by this new Duke Cancer Institute research, which suggests lasofoxifene’s potential as a viable immunotherapy combination agent across a broad spectrum of cancer types,” said Dr. David Portman, Sermonix chief executive officer. “With our Phase 3 ELAINE-3 trial currently investigating the combination of lasofoxifene and abemaciclib in the ESR1-mutated metastatic breast cancer setting, and other data suggesting lasofoxifene’s differentiated and positive influence on genitourinary syndrome of menopause, sexual function and bone health, Duke’s research further demonstrates the need to continue examining the drug’s potential as an effective therapy in combination with other treatments to help patients confront cancer.”

Eosinophils, the white blood cells analyzed in the study, were recently identified as influential in combating tumor progression. A phenomenon called tumor associated tissue eosinophilia (TATE) is linked to better outcomes among patients with multiple types of cancer, including colon, esophageal, gastric, oral, melanoma and liver cancers.

In the article, researchers describe how estrogens not only decrease TATE and the ability of the immune system to attack tumors, but also reduce the effectiveness of immunotherapies that are used to treat many types of cancers, including triple-negative breast cancer (TNBC). TNBC is an aggressive form of disease that is negative for estrogen, progesterone and the HER2 receptor proteins. The researchers found that lasofoxifene was more efficacious than fulvestrant in reversing the detrimental effects of estrogens on tumor-associated eosinophilia and restoring potency to immunotherapies in a TNBC mouse model.

“Lasofoxifene, which demonstrated superior efficacy than fulvestrant, also has been shown to be a well tolerated oral therapy in multiple clinical studies, making it a promising regulator of TATE/tumor growth,” said senior author Donald McDonnell, PhD, Professor in the Departments of Medicine, Pharmacology and Cancer Biology, and Cell Biology at Duke University School of Medicine. “The primary goal of our research is to develop ways to increase the anti-cancer activity of immunotherapies, and we look forward to further studying the lasofoxifene’s potential in this arena.”

Sermonix licensed patents from Duke covering the use of lasofoxifene in ESR1-mutated breast cancers. It also holds options on additional US patent applications covering the use of lasofoxifene to enhance TATE and efficacy of immunotherapy in different cancers.

Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc., has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy, could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

Sermonix Pharmaceuticals Inc. is a privately held biopharmaceutical company focused on the development of female-specific oncology products and is currently undertaking a Phase 3 clinical study of lasofoxifene, its lead investigational drug. The Sermonix management team, led by founder Dr. David Portman, has significant experience in all stages of the drug development, regulatory and commercialization processes. Paul Plourde, M.D., vice president of oncology clinical development, has many decades of experience at AstraZeneca in the breast cancer drug development arena. Barry Komm, Ph.D., chief scientific officer, is recognized for his expertise in nuclear receptor biology. Miriam Portman, M.D., is co-founder and chief operating officer, with expertise in clinical trial conduct and patient recruitment. Elizabeth Attias, MMSc, ScD., chief strategy and development officer, has extensive experience in pharmaceutical drug commercialization. Simon Jenkins, PhD, vice president of operations, has over 30 years of experience in global drug development leadership. Sermonix non-executive chairman of the board is Anthony Wild, Ph.D., former president of both Parke-Davis Pharmaceuticals and Warner-Lambert’s Pharmaceutical Division. Learn more at SermonixPharma.com. To learn more about the ELAINE studies, visit DiscoverElaine.com.